20.500.12556/RUL-161033 High burden of clonal mast cell disorders and hereditary α-tryptasemia in patients who need Hymenoptera venom immunotherapy Background: In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT. Methods: 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. Results: 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n= 207 of 610] with Ring-Messmer grade 3–4 vs. 11% [n= 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n= 2 of 152) of controls with LLR and none with asymptomatic sensitization (n= 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n= 207] in Grade 3–4 vs. 0.001% [n= 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n= 196 of 285]). All KIT p.D816V-positive individuals (n= 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p <  .01), and remarkably, 31.0% (n= 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01). Conclusions: By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT. anaphylaxis hereditary α-tryptasemia hypersensitivity immunotherapy mast cell mastocytosis venom anafilaksija dedna α-triptazemija preobčutljivost imunoterapija mastociti mastocitoza strupi kožekrilcev true false true Angleški jezik Slovenski jezik Članek v reviji 2024-09-06 09:48:00 2024-09-06 09:48:01 2025-08-08 13:33:35 0000-00-00 00:00:00 2024 0 0 Str. 2458-2469 iss 9 Vol. 79 Sep. 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-097 1398-9995 10.1111/all.16084 190093315 Allergy_-_2024_-_Korosec_-_High_burden_of_clonal_mast_cell_disorders_and_hereditary__‐tryptasemia_in_patients_who_need.pdf Allergy_-_2024_-_Korosec_-_High_burden_of_clonal_mast_cell_disorders_and_hereditary__‐tryptasemia_in_patients_who_need.pdf 1 BD421B5F28F9F04BF4DA3D228E9ECD11 8e5c9cbcc10b7cab69f44aa81f3a15e12be705daa9f115baadadc86f5de58bbe 4b2681ee-6c25-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=189888 https://onlinelibrary.wiley.com/doi/10.1111/all.16084 0 ff701437-6c24-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=189886 Fakulteta za farmacijo Biotehniška fakulteta Medicinska fakulteta 0 0 0